Hypokalemia is one of the most common electrolyte disorders in clinical practice and can be observed in as many as 20% of hospitalized patients. The most frequent causes of hypokalemia include administration of diuretic drugs, surreptitious vomiting (e.g., bulimia), and severe diarrhea. Gitelman syndrome (a genetic defect in the Na+/ Cl− symporter in the apical membrane of distal tubule cells) also causes hypokalemia (see Chapter 36). Hyperkalemia is also a common electrolyte disorder and is seen in 1% to 10% of hospitalized patients. Hyperkalemia often occurs in patients with renal failure, in patients taking drugs such as angiotensin-converting enzyme (ACE) inhibitors and K+-sparing diuretics, in patients with hyperglycemia (i.e., high blood sugar), and in the elderly. Pseudohyperkalemia, a falsely high plasma [K+], is caused by traumatic lysis of red blood cells during blood drawing. Red blood cells, like all cells, contain K+ , and lysis of red blood cells releases K+ into plasma, thereby artificially elevating plasma [K+].
The large concentration difference of K+ across cell membranes (≈146 mEq/L) is maintained by the operation of Na+,K+-ATPase. This [K+] gradient is important in • Fig. 36.2 Electrocardiographs from individuals with varying plasma • Fig. 36.1 Effects of variations in plasma [K+] on resting membrane potential of skeletal muscle. Hyperkalemia causes membrane potential to become less negative, which decreases excitability by inactivating the fast Na+ channels responsible for the depolarizing phase of the action potential. Hypokalemia hyperpolarizes the membrane potential and thereby reduces excitability because a larger stimulus is required to depolarize the membrane potential to the threshold potential. Resting indicates “normal” resting membrane potential. Normal threshold indicates the membrane threshold potential.
maintaining the potential difference across cell membranes. Thus K+ is critical for the excitability of nerve and muscle cells, as well as for the contractility of cardiac, skeletal, and smooth muscle cells (
Fig. 36.1 [K+]. See text for details. (Modified from Barker L et al. Principles of Ambulatory Medicine. 5th ed. Baltimore: Williams & Wilkins; 1999.)
This rise in plasma [K+], which could have deleterious effects on the electrical activity of the heart and other excitable tissues, is prevented by the rapid (minutes) uptake of K+ into cells. Because excretion of K+ by the kidneys
Cardiac arrhythmias are produced by both hypokalemia and hyperkalemia. The electrocardiogram (ECG;
Fig. 36.2 ) monitors the electrical activity of the heart and is a fast and easy way to determine whether changes in plasma [K+] influence the heart and other excitable cells. In contrast, measurement of plasma [K+] by the clinical laboratory requires a blood sample, and values are often not immediately available. The first sign of hyperkalemia is the appearance of tall, thin T waves on the ECG. Further increases in plasma [K+] prolong the PR interval, depress the ST segment, and lengthen the QRS interval of the ECG. Finally, as plasma [K+] approaches 10 mEq/L, the P wave disappears, the QRS interval broadens, the ECG appears as a sine wave, and the ventricles fibrillate (i.e., manifest rapid, uncoordinated contractions of muscle fibers). Hypokalemia prolongs the QT interval, inverts the T wave, and lowers the ST segment of the ECG.